Dr. Eric N. Taylor hopes to become a physician-scientist who will make substantial, lasting contributions to the care of patients with renal disease. A mentored career development award will allow Dr. Taylor to develop the following prerequisites for a successful career as an independent clinical investigator: 1) advanced skills in biostatistics and epidemiology; 2) protected time to pursue a focused research program; and 3) close, long-term mentorship by experienced, successful clinical investigators. Dr. Taylor's research interest is nephrolithiasis, which is a common, costly, and painful disease. The goals of this proposal are to resolve controversies in the field of nutrition and nephrolithiasis and to identify novel lifestyle, hormonal, and genetic risk factors for kidney stone formation. Using a prospective study design, he will examine the association between specific dietary and lifestyle factors and the risk of symptomatic kidney stone formation in three large cohorts: the Health Professionals Follow-up Study (N=51,000 men), the Nurses' Health Study I (N= 121,000 older women), and the Nurses' Health Study II (N=116,000 younger women). These factors include the dietary intake of oxalate, non-dairy calcium, and phytate, and the use of non-steroidal anti-inflammatory drugs (NSAIDs). In addition, he will study the relation between insulin resistance, as assessed by fasting levels of plasma insulin, and the risk of kidney stone formation using a nested case-control design (N=1500). He also will examine the association between specific polymorphisms of the vitamin D receptor and the calcium-sensing receptor genes and the risk of incident nephrolithiasis (N=3000). Finally, he will examine the effect of these genetic polymorphisms on the 24-hour urinary excretion of calcium (N=1500). Overall, Dr. Taylor anticipates that his research will result in better strategies to prevent stone disease. In addition to providing Dr. Taylor a unique opportunity to develop experience and expertise in the study of risk factors for kidney stone formation, the career development award will allow him to become proficient with advanced epidemiologic and analytic techniques. At the completion of this career development award, Dr. Taylor will have a unique combination of skills and experience that will enable him to succeed as an independent clinical investigator.